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Binding sites on G-protein Coupled Receptors
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Basic concepts about ligand -receptor interactions, especially involving GPCRs, are summarized in Chapter 1, while in Chapter 2 the experimental and theoretical techniques used in this work are described. That includes the use of laboratory animals, cell fractionations, radioligand binding assay, pharmacodynamic mathematical models, chemical synthesis and the use of computer in drug discovery and molecular pharmacology. These techniques were exploited in order to investigate interactions between bivalent ligands and GPCRs as a function of the molecular size. A simple model was proposes and validated by means of newly synthesized dimeric theophylline derivatives tested on adenosine A1 receptors (Chapter 3). Moreover, they were exploited in the development of a new mathematical model for more complex interactions at the GPCRs, which as been referred to as Enhancer and Competitive Allosteric Modulator (ECAM) model (Chapter 4). Finally, Chapter 5 reminds general conclusions obtained from the present work, also giving an overview about future perspectives. The last chapter (Chapter 6) gives a summary of this study.
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